Objective: To evaluate emotional distress, depression and quality of life in parents of infants with severe congenital heart disease (CHD) during their first hospitalization. Methods: A pilot study for 38 parental couples of infants with CHD hospitalized within the 3 months of life. Parents filled up three self-administered questionnaires. We compared differences in the variables measuring emotional distress, depression and quality of life between mothers and fathers, and between prenatal and postnatal diagnosis. Results: Stress and depression levels were significantly higher in mothers than in fathers (stress: 81.8% mothers versus 60.6% fathers; depression: 45.7% mothers versus 20.0% fathers). No difference were found between prenatal and postnatal groups in any field tested but, in percentage, mothers receiving prenatal diagnosis were more depressed, whereas those receiving postnatal diagnosis were more stressed. Fathers showed same tendency. Conclusions: Parents of newborns with severe CHD, especially mothers, need psychological support during their child’s hospitalization. Parents of children diagnosed prenatally may need counseling throughout pregnancy to help them recover from the loss of the imagined healthy child.